Transmembrane protein with EGF-like and two follistatin-like domains 1 (TMEFF1)

Transmembrane protein with EGF-like and two follistatin-like domains 1 (TMEFF1, also known as Tomoregulin-1) is a single-pass transmembrane protein containing extracellular epidermal growth factor (EGF)-like and two follistatin-like modules[1][2]. TMEFF1 is highly expressed in the nervous system and embryonic tissues and is involved in developmental processes and cell differentiation[1]. In cancer biology, TMEFF1 displays context-dependent roles: it shows anti-tumor effects in brain tumors but acts as a tumor-promoting gene in ovarian cancer by driving cellular proliferation, migration, and invasion, and inhibiting apoptosis, likely via activation of the MAPK and PI3K/AKT signaling pathways[1]. TMEFF1 also regulates the epithelial–mesenchymal transition (EMT), influencing cancer cell metastasis and stemness[1]. Mechanistically, TMEFF1 can bind to the nodal co-receptor Cripto-1, thereby blocking nodal but not activin signaling in the TGF-β pathway; this occurs at the cell membrane and is required for certain embryogenesis and axis formation processes[2]. Additionally, TMEFF1 has been described as a viral restriction factor in the human brain, protecting neurons against viral entry[3]. It is being investigated as a potential biomarker and therapeutic target, especially for certain cancers, although no drug interactions or direct therapeutic agents are described to date.

Other names

Tomoregulin-1TR-1C9orf2H7365CT120.1cancer/testis antigen family 120 member 1

Modulates MAPK and PI3K/AKT signaling pathways. Binds Cripto-1 to block nodal signaling of TGF-β family. Influences EMT marker expression.